Ketamine Inhibits Maturation of Bone Marrow-Derived Dendritic Cells and Priming of the Th1-Type Immune Response
Ketamine Inhibits Maturation of Bone Marrow-Derived Dendritic Cells and Priming of the Th1-Type Immune Response
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DOI：
10.1213/ane.0b013e3181adc384
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发表时间：
2009-09-01
影响因子：
5.7
通讯作者：
Fujino, Yuji
中科院分区：
文献类型：
--
作者：
Ohta, Noriyuki;Ohashi, Yoshifumi;Fujino, Yuji
背景技术背景：树突状细胞（DC）作为抗原递呈细胞发挥着关键作用，越来越多的证据表明DC影响T细胞活化并调节免疫反应的极性。据报道，氯胺酮具有影响免疫细胞（包括巨噬细胞和自然杀伤细胞）的免疫调节特性。然而，氯胺酮对DC的作用尚未被表征。方法：采用粒细胞-单核细胞集落刺激因子（GM-CSF）和白细胞介素（IL）-4（IL-4）诱导骨髓来源的DC，分析其共刺激分子（CD 40、CD 80和CD 86）、主要组织相容性复合物II类分子的表达和IL-12 p40的分泌。此外，我们评估了混合细胞培养的DC和T细胞的免疫反应和接触性超敏反应在整个animal.Results：氯胺酮抑制CD 40，CD 80，和主要组织相容性复合物11类分子在DC中的表达。用氯胺酮处理的DC也分泌较少的IL-12 p40并显示出更大的内吞作用。在CD 4（+）T细胞和DC的混合细胞培养物中，氯胺酮处理的DC显示刺激CD 4（+）T细胞增殖和从CD 4（+）T细胞分泌干扰素的倾向较低。此外，氯胺酮处理的DCs损害诱导的细胞介导的免疫respons.CONCLUSION：我们的研究结果表明，氯胺酮抑制功能成熟的DCs和干扰DC诱导的Th 1免疫在整个动物。这些新的发现为氯胺酮的免疫药理学作用提供了新的见解。（Anesth Analg 2009：109：793-800）
BACKGROUND: Dendritic cells (DCs) play a key role as antigen-presenting cells and growing evidence Suggests that DCs influence T-cell activation and regulate the polarity of the immune response. Ketamine has been reported to have immunomodulatory properties that affect immune cells, including macrophages and natural killer cells. However, the effect of ketamine on DCs has not been characterized. We examined the immunomodulation of DCs by ketamine.METHODS: We used bone marrow-derived DCs induced by granulocyte-monocytecolony stimulating factor and interleukin (IL)-4 from bone marrow and analyzed the expression of costimulatory molecules (CD40, CD80, and CD86), major histocompatibility complex class II molecules, and secretion of IL-12p40. Furthermore, we evaluated the immune response in mixed cell cultures of DCs and T cells and the contact hypersensitivity response in a whole animal.RESULTS: Ketamin suppressed the expression of CD40, CD80, and major histocompatibility complex class 11 molecules in DCs. DCs treated with ketamine also secreted less IL-12p40 and displayed greater endocytosis. In mixed cell cultures with CD4(+) T cells and DCs, ketamine-treated DCs showed less propensity to stimulate the proliferation of CD4(+) T cells and the secretion of interferon from CD4(+) T cells. Furthermore, ketamine-treated DCs impaired the induction Of a cell-mediated immune response.CONCLUSION: Our findings suggest that ketamine inhibits the functional maturation of DCs and interferes with DC induction of Th1 immunity in the whole animal. These novel findings provide new insight into the immunopharmacological role of ketamine. (Anesth Analg 2009:109:793-800)